Conditioned medium of human adipose-derived mesenchymal stem cells mediates protection in neurons following glutamate excitotoxicity by regulating energy metabolism and GAP-43 expression.
Metab Brain Dis
; 29(1): 193-205, 2014 Mar.
Article
en En
| MEDLINE
| ID: mdl-24458787
Glutamate excitotoxicity has been implicated as one of the pathological mechanisms contributing to neuronal cell death and is involved in many neurological disorders. Stem cell transplantation is a promising approach for the treatment of nervous system damage or diseases. Previous studies have shown that mesenchymal stem cells (MSCs) have important therapeutic effects in experimental animal and preclinical disease model of central nervous system pathology. However, it is not well understood whether neurogenesis of MSCs or MSC conditioned-medium (CM) containing microparticles mediates therapeutic effects. Here, we investigated the neuroprotective effects of human adipose-derived MSCs (AMSCs) on cortical neurons using models of glutamate excitotoxicity. Following exposure to glutamate (100 µM, 15 min), cortical neurons were co-cultured with either AMSCs separated by a semiporous membrane (prohibiting direct cell-cell contact) or with AMSC-CM for 18 h. Compared to untreated control groups, AMSCs and AMSC-CM partially and similarly reduced neuronal cell damages, as indicated by reduced LDH release, a decreased number of trypan-positive cells and a decline in the number of apoptotic nuclei. Protection by CM was associated with increased GAP-43 expression and an elevated number of GAP-43-positive neurites. Furthermore, CM increased levels of ATP, NAD(+) and NADH and the ratio of NAD(+)/NADH, while preventing a glutamate-induced decline in mitochondrial membrane potential. These results demonstrate that AMSC-CM mediates direct neuroprotection by inhibiting neuronal cell damage/apoptosis, promoting nerve regeneration and repair, and restoring bioenergy following energy depletion caused by glutamate excitotoxicity.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tejido Adiposo
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Ácido Glutámico
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Proteína GAP-43
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Metabolismo Energético
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Células Madre Mesenquimatosas
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Neuronas
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Neurotoxinas
Límite:
Adult
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Animals
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Humans
Idioma:
En
Revista:
Metab Brain Dis
Asunto de la revista:
CEREBRO
/
METABOLISMO
Año:
2014
Tipo del documento:
Article
Pais de publicación:
Estados Unidos